Magnolol (5,5′-diallylbiphenyl-2,2′-diol or 5,5′-dially-2,2′-bisphenol), together with honokiol, are the major ingredients found in magnolia extracts. It is well recognized in the art that magnolia extracts have found, among other things, applications in compositions to treat bacteria and/or inflammation related oral diseases. See, e.g., U.S. Pat. No. 6,544.409, and U.S. patent application publication No. U.S. 2006/0,140,885, the disclosures of which are incorporated by reference herein in their entireties.

Studies have further revealed that magnolol, as an independent active substance, also plays an important role in other pharmacological processes besides its anti-bacterial and anti-inflammatory activities. For example, magnolol has been shown to exhibit a beneficial capability of protecting the myocardium against infarction and reperfusion injury. It has also been shown that magnolol protects neurons against chemical hypoxia by KCN in cortical neuron-astrocyte mixed cultures. More recently, it is reported, that magnolol possesses an antioxidant activity 1000 times greater than α-tocopherol, implicating magnolol's great potential in food and pharmaceutical applications. All these divergent uses reveal that there is a great need for high quality and affordable magnolol. See Wen-Hsin Huang et al., The Chinese Pharmaceutical Journal, 2006, 58, 115-122; Min-Min Lee et al. Chinese Journal of Physiology, 2000, 43, 61-67.
Currently, there are several synthetic methods of producing magnolol reported in the art, one of which is described in a paper by J. Runeberg, Acta Chem Scand, 1958, 12, 188-192, wherein the key reactant, methyl ether of 5,5′-dibromo-2,2′-bisphenol was reacted with allyl bromide in tetrahydrofuran (THF) in the presence of ethylmagnesium bromide to obtain methyl ether of 5.5′-diallylbiphenyl-2,2-diol as shown below:

This reaction requires refluxing conditions, and provides a low yield of the desired product. Furthermore, the subsequent step of removing the methyl group of methyl ether of 5,5′-diallylbiphenyl-2,2′-diol to obtain magnolol requires even higher temperature, and the reaction mixture is difficult to separate and purify, thereby resulting in a low yield of magnolol.
Other reported synthetic methods of producing magnolol in the art also suffer similar problems such as low yields, difficulty in purification, the high cost of synthesis, and/or not practical or compatible for industrial scale. See, e.g., Wen-Hsin Huang et al., The Chinese Pharmaceutical Journal, 2006, 58, 115-122; and Wenxin On et al., Tetrahedron: Asymmetry, 1998, 9, 1377-1380. Therefore, there exists a practical need in the art to develop a synthetic method to produce high quality and affordable magnolol, as well as derivatives and analogues thereof.